International Journal of Tryptophan Research最新文献

{"title":"Does Exercise Influence Kynurenine/Tryptophan Metabolism and Psychological Outcomes in Persons With Age-Related Diseases? A Systematic Review.","authors":"Anthony Lim,&nbsp;Christel Harijanto,&nbsp;Sara Vogrin,&nbsp;Gilles Guillemin,&nbsp;Gustavo Duque","doi":"10.1177/1178646921991119","DOIUrl":"https://doi.org/10.1177/1178646921991119","url":null,"abstract":"<p><strong>Background: </strong>The kynurenine (KYN) pathway has been implicated in many diseases associated with inflammation and aging (\"inflammaging\"). Targeting the kynurenine pathway to modify disease outcomes has been trialled pharmacologically, but the evidence of non-pharmacological means (ie, exercise) remains unclear.</p><p><strong>Objective: </strong>We aim to assess the evidence of the effects of exercise on the kynurenine pathway and psychological outcomes.</p><p><strong>Methods: </strong>Under Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, a systematic literature search was performed in MEDLINE, EMBASE, EMCARE, and the Cochrane Central Registry of Controlled Trials. The main outcomes were changes in kynurenine pathway metabolite levels and psychological outcomes.</p><p><strong>Results: </strong>Six studies were analyzed (total n = 379) with exercise demonstrating significant concomitant effects on kynurenine pathway metabolite levels and associated psychological outcomes in domains of somatization, anxiety, and depression.</p><p><strong>Conclusion: </strong>Exercise has significant concomitant effect on kynurenine pathway metabolite levels and psychological outcomes. However, clear limitations exist in determining if the changes in the kynurenine pathway can fully explain the changes in psychological outcomes, or whether different diseases and exercise interventions act as confounding factors.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"14 ","pages":"1178646921991119"},"PeriodicalIF":4.4,"publicationDate":"2021-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646921991119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25389905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Localization of Indoleamine 2,3-Dioxygenase-1 and Indoleamine 2,3-Dioxygenase-2 at the Human Maternal-Fetal Interface.","authors":"Yoshiki Kudo,&nbsp;Iemasa Koh,&nbsp;Jun Sugimoto","doi":"10.1177/1178646920984163","DOIUrl":"https://doi.org/10.1177/1178646920984163","url":null,"abstract":"<p><p>Immunohistochemical localization of indoleamine 2,3-dioxygenase-1 and indoleamine 2,3-dioxygenase-2, the first and rate-limiting enzyme in tryptophan metabolism along the kynurenine pathway, has been studied in order to better understand the physiological significance of these enzymes at the maternal-fetal interface of human pregnancy with a gestational age of 7 weeks (n = 1) and term placentas (37-40 weeks of gestation, n = 5). Indoleamine 2,3-dioxygenase-1 protein immunoreactivity was found in glandular epithelium of the decidua and the endothelium of the fetal blood vessels in the villous stroma with some additional positive cells in the villous core and in the decidua. The syncytiotrophoblast stained strongly for indoleamine 2,3-dioxygenase-2. Immunoreactivity of kynurenine, the immediate downstream product of indoleamine 2,3-dioxygenase-mediated tryptophan metabolism, showed the same localization as that of indoleamine 2,3-dioxygenase-1 and indoleamine 2,3-dioxygenase-2, suggesting these are functional enzymes. Interferon-γ added to placental villous explant culture markedly stimulated expression level of both mRNA and immunoreactivity of indoleamine 2,3-dioxygenase-1. The different cellular expression and interferon-γ sensitivity of these enzymes at the maternal-fetal interface suggests distinct physiological roles for each enzyme in normal human viviparity.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"13 ","pages":"1178646920984163"},"PeriodicalIF":4.4,"publicationDate":"2020-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646920984163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38824110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium Butyrate and Indole-3-propionic Acid Prevent the Increase of Cytokines and Kynurenine Levels in LPS-induced Human Primary Astrocytes.","authors":"Michelle L Garcez,&nbsp;Vanessa X Tan,&nbsp;Benjamin Heng,&nbsp;Gilles J Guillemin","doi":"10.1177/1178646920978404","DOIUrl":"https://doi.org/10.1177/1178646920978404","url":null,"abstract":"<p><p>The crosstalk between central nervous system (CNS) and gut microbiota plays key roles in neuroinflammation and chronic immune activation that are common features of all neurodegenerative diseases. Imbalance in the microbiota can lead to an increase in the intestinal permeability allowing toxins to diffuse and reach the CNS, as well as impairing the production of neuroprotective metabolites such as sodium butyrate (SB) and indole-3-propionic acid (IPA). The aim of the present study was to evaluate the effect of SB and IPA on LPS-induced production of cytokines and tryptophan metabolites in human astrocytes. Primary cultures of human astrocytes were pre-incubated with SB or IPA for 1 hour before treatment with LPS. Cell viability was not affected at 24, 48 or 72 hours after pre-treatment with SB, IPA or LPS treatment. SB was able to significantly prevent the increase of GM-CSF, MCP-1, IL-6 IL-12, and IL-13 triggered by LPS. SB and IPA also prevented inflammation indicated by the increase in kynurenine and kynurenine/tryptophan ratio induced by LPS treatment. IPA pre-treatment prevented the LPS-induced increase in MCP-1, IL-12, IL-13, and TNF-α levels 24 hours after pre-treatment, but had no effect on tryptophan metabolites. The present study showed for the first time that bacterial metabolites SB and IPA have potential anti-inflammatory effect on primary human astrocytes with potential therapeutic benefit in neurodegenerative disease characterized by the presence of chronic low-grade inflammation.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"13 ","pages":"1178646920978404"},"PeriodicalIF":4.4,"publicationDate":"2020-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646920978404","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38824109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Tryptophan 2,3-Dioxygenase Inhibition on Kynurenine Metabolism and Cognitive Function in the APP23 Mouse Model of Alzheimer's Disease.","authors":"Fjh Sorgdrager,&nbsp;C P van Der Ley,&nbsp;M van Faassen,&nbsp;E Calus,&nbsp;E A Nollen,&nbsp;I P Kema,&nbsp;D van Dam,&nbsp;P P De Deyn","doi":"10.1177/1178646920972657","DOIUrl":"https://doi.org/10.1177/1178646920972657","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is associated with progressive endogenous neurotoxicity and hampered inflammatory regulation. The kynurenine (Kyn) pathway, which is controlled by tryptophan 2,3-dioxygenase (TDO), produces neuroactive and anti-inflammatory metabolites. Age-related Kyn pathway activation might contribute to AD pathology in humans, and inhibition of TDO was found to reduce AD-related cellular toxicity and behavioral deficits in animal models. To further explore the effect of aging on the Kyn pathway in the context of AD, we analyzed Kyn metabolite profiles in serum and brain tissue of the APP23 amyloidosis mouse model. We found that aging had genotype-independent effects on Kyn metabolite profiles in serum, cortex, hippocampus and cerebellum, whereas serum concentrations of many Kyn metabolites were reduced in APP23 mice. Next, to further establish the role of TDO in AD-related behavioral deficits, we investigated the effect of long-term pharmacological TDO inhibition on cognitive performance in APP23 mice. Our results indicated that TDO inhibition reversed recognition memory deficits without producing measurable changes in cerebral Kyn metabolites. TDO inhibition did not affect spatial learning and memory or anxiety-related behavior. These data indicate that age-related Kyn pathway activation is not specific for humans and could represent a cross-species phenotype of aging. These data warrant further investigation on the role of peripheral Kyn pathway disturbances and cerebral TDO activity in AD pathophysiology.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"13 ","pages":"1178646920972657"},"PeriodicalIF":4.4,"publicationDate":"2020-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646920972657","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38824108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social and Biological Parameters Involved in Suicide Ideation During the COVID-19 Pandemic: A Narrative Review.","authors":"Chenthamara Dhrisya, Murugan Prasathkumar, Robert Becky, Salim Anisha, Subramaniam Sadhasivam, Musthafa Mohamed Essa, Saravana Babu Chidambaram, Buthainah Al-Balushi, Gilles J Guillemin, M Walid Qoronfleh","doi":"10.1177/1178646920978243","DOIUrl":"10.1177/1178646920978243","url":null,"abstract":"<p><p>Fear is an indispensable characteristic of any infectious disease, and the alarm will be further amplified when the infection spreads uncontrollable, unpredictable, and global. The novel corona virus (SARS CoV-2) lead Covid-19, has been declared as a global emergency by WHO as it has affected millions of people with a high mortality rate. The non-availability of medicine for Covid-19 and the various control measures such as social distancing, self-isolation, house quarantine, and the new normal implementation by different nations across the world to control the spread of Covid-19 made people vulnerable to fear and anxiety. As a result, considerable number of Covid-19-related suicidal deaths has been reported across the world during this pandemic. There have been several studies which describe the psychosocial aspects of suicidal ideation. However, the research on the biological aspects of suicidal ideation/suicidal risk factors that are related to pandemic are unreported. Hence this review article is intended to provide a comprehensive analysis of suicidal deaths during Covid-19 and also aimed to addresses the possible link between suicidal ideation and different factors, including psycho-social, behavioral, neurobiological factors (proximal, distal, and inflammatory) and immunity. The alterations in glutamatergic and GABAergic neurotransmitters had upregulated the GABARB3, GABARA4, GABARA3, GABARR1, GABARG2, and GAD2 gene expressions in suicidal victims. The changes in the Kynurenine (KYN) pathway, Hypothalamus-Pituitary-Adrenal axis (HPA axis) hyperactivation, and dysregulation of serotonin biosynthesis would significantly alter the brain chemistry in people with suicide ideation.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"13 ","pages":"1178646920978243"},"PeriodicalIF":2.7,"publicationDate":"2020-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b4/8a/10.1177_1178646920978243.PMC8851148.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39814407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Saturated Fatty Acid Intake Is Associated With Increased Inflammation, Conversion of Kynurenine to Tryptophan, and Delta-9 Desaturase Activity in Healthy Humans.","authors":"Jade Berg,&nbsp;Neda Seyedsadjadi,&nbsp;Ross Grant","doi":"10.1177/1178646920981946","DOIUrl":"https://doi.org/10.1177/1178646920981946","url":null,"abstract":"<p><p>Saturated fat ingestion has previously been linked to increases in inflammation. However the relationship between saturated fatty acid (SFA) intake and the kynureine:tryptophan ratio ([Kyn]:[Trp]), a marker of inflammation, has not been previously investigated. This study evaluated in healthy, middle aged, individuals (men = 48, women = 52), potential relationships between SFA intake, red blood cell (RBC) membrane SFAs and monounsaturated fatty acids (MUFA), the [Kyn]:[Trp] ratio, C-reactive protein (CRP), TNF-α and Δ9 desaturase activity. [Kyn]:[Trp] was positively associated with increases in Total fat (<i>P</i> = .034) intake, including Total SFA (<i>P</i> = .029) and Total MUFA (<i>P</i> = .042) intakes. Unexpectedly the [Kyn]:[Trp] ratio was inversely associated with the percentage of Total SFA (<i>P</i> = .004) and positively associated with percentage of Total MUFA (<i>P</i> = .012) present in the RBC membrane. We found a positive association between Δ9 desaturase activity, responsible for the desaturation of a various SFAs to MUFAs, and [Kyn]:[Trp] (<i>P</i> = .008). [Kyn]:[Trp] was also positively associated with CRP (<i>P</i> = .044), however no significant relationship between [Kyn]:[Trp] and TNF-α was found. This study shows for the first time that SFA consumption increases inflammatory pathways linked to increased tryptophan to kynurenine conversion, even in healthy humans. Our data also suggests that SFA linked increases in inflammation occur concomitantly with an upregulation of Δ9 desaturase activity resulting in increased desaturation of SFA substrates to their MUFA derivatives.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"13 ","pages":"1178646920981946"},"PeriodicalIF":4.4,"publicationDate":"2020-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646920981946","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38793931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In Silico</i> ADME, Metabolism Prediction and Hydrolysis Study of Melatonin Derivatives.","authors":"Panyada Panyatip,&nbsp;Nadtanet Nunthaboot,&nbsp;Ploenthip Puthongking","doi":"10.1177/1178646920978245","DOIUrl":"https://doi.org/10.1177/1178646920978245","url":null,"abstract":"<p><p>Melatonin (MLT) is a well-known pineal hormone possessed with remarkable biological activities. However, its low oral bioavailability and high first-pass metabolism rate are important pharmacokinetics problems. Therefore, 5 MLT derivatives (<b>1</b>-<b>5</b>) were designed and synthesised in our group to solve these problems. In this work, <i>in silico</i> analysis of all synthetic derivatives for pharmacokinetic and drug-likeness parameters were predicted by SwissADME software. The results revealed that all derivatives (<b>1</b>-<b>5</b>) met the requirements for ideal oral bioavailability and CNS drugs. The molecular docking showed that the acetyl-MLT derivative (<b>1</b>) and the un-substitution at <i>N1</i>-position derivative <b>5</b> would be substrates of CYP1A2, while the lipophilic substituted <i>N1</i>-position derivatives <b>2</b>-<b>4</b> could not be metabolised by CYP1A2. Moreover, all <i>N</i>-amide derivatives (<b>1</b>-<b>4</b>) were hydrolysed and released less than 2.33% MLT after 4-hour incubation in 80% human plasma. It seemed that these derivatives preferred to behave like drugs rather than prodrugs of MLT. These findings confirmed that the addition of bulky groups at the <i>N1</i>-position of the MLT core could prolong the half-life, increase drug absorption and penetrate the blood brain barrier into the CNS.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"13 ","pages":"1178646920978245"},"PeriodicalIF":4.4,"publicationDate":"2020-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646920978245","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38785223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantification of Plasma Kynurenine Metabolites Following One Bout of Sprint Interval Exercise.","authors":"Ada Trepci, Sophie Imbeault, Victoria L Wyckelsma, Håkan Westerblad, Sigurd Hermansson, Daniel C Andersson, Fredrik Piehl, Tomas Venckunas, Marius Brazaitis, Sigitas Kamandulis, Lena Brundin, Sophie Erhardt, Lilly Schwieler","doi":"10.1177/1178646920978241","DOIUrl":"10.1177/1178646920978241","url":null,"abstract":"<p><p>The kynurenine pathway of tryptophan degradation produces several neuroactive metabolites suggested to be involved in a wide variety of diseases and disorders, however, technical challenges in reliably detecting these metabolites hampers cross-comparisons. The main objective of this study was to develop an accurate, robust and precise bioanalytical method for simultaneous quantification of ten plasma kynurenine metabolites. As a secondary aim, we applied this method on blood samples taken from healthy subjects conducting 1 session of sprint interval exercise (SIE). It is well accepted that physical exercise is associated with health benefits and reduces risks of psychiatric illness, diabetes, cancer and cardiovascular disease, but also influences the peripheral and central concentrations of kynurenines. In line with this, we found that in healthy old adults (<i>n</i> = 10; mean age 64 years), levels of kynurenine increased 1 hour (<i>P</i> = .03) after SIE, while kynurenic acid (KYNA) concentrations were elevated after 24 hours (<i>P</i> = .02). In contrast, no significant changes after exercise were seen in young adults (<i>n</i> = 10; mean age 24 years). In conclusion, the described method performs well in reliably detecting all the analyzed metabolites in plasma samples. Furthermore, we also detected an age-dependent effect on the degree by which a single intense training session affects kynurenine metabolite levels.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"13 ","pages":"1178646920978241"},"PeriodicalIF":4.4,"publicationDate":"2020-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38743900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alteration in Gene Pair Correlations in Tryptophan Metabolism as a Hallmark in Cancer Diagnosis.","authors":"Meena Kishore Sakharkar,&nbsp;Sarinder Kaur Dhillon,&nbsp;Karthic Rajamanickam,&nbsp;Benjamin Heng,&nbsp;Nady Braidy,&nbsp;Gilles J Guillemin,&nbsp;Jian Yang","doi":"10.1177/1178646920977013","DOIUrl":"https://doi.org/10.1177/1178646920977013","url":null,"abstract":"<p><p>Tryptophan metabolism plays essential roles in both immunomodulation and cancer development. Indoleamine 2,3-dioxygenase, a rate-limiting enzyme in the metabolic pathway, is overexpressed in different types of cancer. To get a better understanding of the involvement of tryptophan metabolism in cancer development, we evaluated the expression and pairwise correlation of 62 genes in the metabolic pathway across 12 types of cancer. Only gene <i>AOX1</i>, encoding aldehyde oxidase 1, was ubiquitously downregulated, Furthermore, we observed that the 62 genes were widely and strongly correlated in normal controls, however, the gene pair correlations were significantly lost in tumor patients for all 12 types of cancer. This implicated that gene pair correlation coefficients of the tryptophan metabolic pathway could be applied as a prognostic and/or diagnostic biomarker for cancer.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"13 ","pages":"1178646920977013"},"PeriodicalIF":4.4,"publicationDate":"2020-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646920977013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38743899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Indoleamine 2,3-Dioxygenase Production and Its Association to Inflammatory Cytokines in Peripheral Blood Mononuclear Cells Culture of Type 2 Diabetes Mellitus.","authors":"Rona Kartika,&nbsp;Heri Wibowo,&nbsp;Dyah Purnamasari,&nbsp;Saraswati Pradipta,&nbsp;Rahma A Larasati","doi":"10.1177/1178646920978236","DOIUrl":"https://doi.org/10.1177/1178646920978236","url":null,"abstract":"<p><strong>Aim: </strong>To analyze indoleamine 2,3-dioxygenase (IDO) production in the cell culture supernatant of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from type 2 DM (T2DM) patients and investigate IDO's association to pro- and anti-inflammatory cytokines.</p><p><strong>Subjects and methods: </strong>PBMC samples were collected from 21 T2DM patients and 17 normoglycemic participants, then stimulated with PHA for 3 days. Cytokine and IDO concentrations were measured in the PBMC culture supernatants. In vitro production of TNF-α, IL-6, interferon-γ, and IL-10 were measured using multiplex immunoassay. IDO concentration was assessed using ELISA. To assess how PHA stimulation altered IDO production and to minimize the unstimulated baseline effect of T2DM, we subtracted the PHA-stimulated IDO concentration from the unstimulated one. IBM SPSS version 23 was used for statistical analysis.</p><p><strong>Results: </strong>The IDO concentrations in the PBMC culture supernatants were significantly higher in T2DM patients regardless of whether they were unstimulated (<i>P</i> < .001) or PHA-stimulated (<i>P</i> = .012). Reduced IDO production was observed in 52.8% of T2DM patients and was associated with older age and lower interferon-γ levels. Conversely, 42.8% of T2DM patients showed increased IDO concentrations, which were correlated with the IL-6/IL-10 ratio (<i>r</i> = 0.683, <i>P</i> = .021) and interferon-γ/IL-10 ratio (<i>r</i> = 0.517, <i>P</i> = .077).</p><p><strong>Conclusion: </strong>The interferon-γ level was reduced in the PBMC culture supernatant of T2DM patients with reduced IDO production. Reduced IDO production in T2DM patients following PHA stimulation was associated with older age and, notably, higher baseline IDO concentrations. Since IDO is primarily produced by dendritic cells, reduced IDO production after PHA stimulation may indicate dendritic cell dysfunction.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"13 ","pages":"1178646920978236"},"PeriodicalIF":4.4,"publicationDate":"2020-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646920978236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38730400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}